Association of Vitamin D with severity and outcome of COVID-19: Clinical and Experimental Evidence

Introduction: The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. Methods: 25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 ARDS into C57/BL6 mice, mice were treated with 0.25 mu g human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured. Results: Vitamin D deficiency and insufficiency were associated with increased severity and unfavourable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNF alpha, IL-6, IFN gamma(sic)and MPO in the lung, as well as down-regulation of pro-inflammatory pathways. Conclusion: Normal levels of endogenous Vitamin D are associated with reduced severity and risk of unfavourable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.